NCT03022825进行中（未招募）2 期
QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 190
- 试验地点
- 27
- 主要终点
- Complete Response
研究概览
简要总结
This is a Phase II/III, open-label, single-arm, multicenter study of intravesical BCG plus N-803 or N-803 only in patients with BCG unresponsive high grade non-muscle invasive bladder cancer (NMIBC). All patients treated in the study will receive via a urinary catheter in the bladder, BCG plus N-803 or N-803 only weekly for 6 consecutive weeks (initial induction treatment period). After the first disease assessment, eligible patients will receive either a 3-week maintenance course or a 6-week re-induction course (second treatment period) at Month 3. Eligible patients will continue to receive maintenance treatment in the third treatment period at Months 6, 9, 12, and 18. Eligible patients have the option to receive maintenance treatment in the fourth treatment period at Months 24, 30, and 36. The study duration is 60 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 18 years of age or older
- •Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).
- •Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1 disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta or T1 disease.
- •Absence of resectable disease after transurethral resection (TURBT) procedures (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergo repeat resection and biopsy [inclusive of muscularis propria] if initial biopsy did not include muscularis propria). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
- •BCG-unresponsive disease as defined as: (a) Persistent or recurrent CIS (+/- recurrent Ta/T1 disease) within 12 months of receiving adequate BCG (at least five of six doses doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (b) Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG (at least five of six doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (c) T1 high-grade disease at the first evaluation following an induction BCG course alone (at least five of six doses of an initial induction course).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
排除标准
- •Recurrence of BCG unresponsive Ta/T1 disease (without presence of CIS) > 6 months after last BCG instillation or BCG unresponsive CIS > 12 months after last BCG instillation.
- •Life expectancy <2 years
- •Any of the following clinical laboratory values at the time of enrollment: (1) Absolute neutrophil count (ANC) <800/µL or (2) Platelets < 50,000/µL
- •Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (AST or ALT) >2 times upper limit of normal (ULN)
- •Renal insufficiency as indicated by a creatinine level >3 times ULN
- •History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer (inclusive of the prostatic urethra); or any other cancer within the past 5 years that is progressing or requires active treatment. Exceptions are adequately treated basal cell or squamous cell skin cancer that has undergone potentially curative therapy or in situ cervical cancer; and adequately treated stage I or II cancer or stable prostate cancer from which the patient is currently in complete remission, and is under active surveillance or hormone control.
- •Symptomatic congestive heart failure (CHF), New York Heart Association (NYHA) Class III or IV heart failure or other clinical signs of severe cardiac dysfunction
- •Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry
- •History or evidence of uncontrollable central nervous system (CNS) disease
- •Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy
- •Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions
- •Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent)
- •Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
- •Patients currently receiving investigational or commercial anti-cancer agents or anti-cancer therapies other than BCG, ALT-803 and supportive care therapies for active disease.
- •Concurrent use of other investigational agents (not including FDA authorized drugs for the prevention and treatment of COVID-19).
- •Other illness or condition, including laboratory abnormalities, which in the opinion of the Investigator would exclude the patient from participating in this study. This includes, but is not limited to, serious medical conditions or psychiatric illness likely to interfere with participation in the study.
研究组 & 干预措施
BCG+N-803
Experimental
干预措施: N-803 and BCG (Drug)
BCG+N-803
Experimental
干预措施: N-803 (Drug)
结局指标
主要结局
Complete Response
时间窗: 60 Months
Cohort A \& Cohort C: Assess incidence of complete response of CIS (with or without Ta/T1 papillary disease) patients at any time
Disease-Free Rate
时间窗: 12 Months
Cohort B: Assess disease-free rate at 12 months since first study treatment
次要结局
- Complete Response(60 months)
- Response(24 months)
研究者
研究点 (27)
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相关资讯
EMA Recommends Conditional Approval for ImmunityBio's Anktiva in BCG-Unresponsive Bladder Cancer- The European Medicines Agency has recommended conditional marketing authorization for Anktiva (nogapendekin alfa inbakicept) combined with BCG for treating BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ.
- Clinical trial data showed a 71% complete response rate in 100 patients, with responses lasting an average of 27 months and ranging up to 54+ months.
- The conditional approval pathway facilitates early access to medicines addressing unmet medical needs, with the decision now moving to the European Commission for final authorization.
- Approximately 150,000 of the 200,000 patients expected to be diagnosed with bladder cancer in Europe in 2025 will have non-muscle invasive disease, representing a significant patient population.9 months agoImmunityBio's Anktiva Pursues European and UK Approval for BCG-Unresponsive Bladder Cancer- ImmunityBio's Anktiva, combined with BCG, seeks approval in the EU and UK for treating BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).
- The MAAs submitted to the EMA and MHRA are supported by Phase 2/3 QUILT-3.032 trial data, demonstrating a 71% complete response rate in patients with NMIBC with CIS.
- Regulatory assessments by both agencies are anticipated to conclude by Q4 2025, potentially leading to approval in Europe and the UK by 2026, expanding global access.
- ImmunityBio also plans to submit a supplemental BLA to the FDA in 2025, seeking approval for Anktiva in patients with BCG-unresponsive NMIBC in the papillary indication.last yearANKTIVA Receives Permanent J-Code from CMS, Streamlining Reimbursement for Bladder Cancer Treatment- The Centers for Medicare & Medicaid Services (CMS) has assigned a permanent J-code (J9028) for ANKTIVA, effective January 1, 2025, to streamline billing.
- ANKTIVA, in combination with BCG, is FDA-approved for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).
- Clinical trial data shows ANKTIVA achieved a 71% complete response rate in patients with BCG-unresponsive NMIBC CIS, with durable responses up to 54 months.last yearAnktiva Plus BCG Shows High Response in BCG-Unresponsive NMIBC- Updated data from the QUILT 3.023 trial shows a 71% complete response rate in patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) treated with Anktiva plus BCG.
- The duration of response in responders ranged up to 54 months, highlighting the potential for cystectomy avoidance in this challenging patient population.
- ImmunityBio plans to submit these data to the European Medicines Agency (EMA) for Marketing Authorization Application (MAA) in Q4 2024.
- The FDA approved Anktiva in April 2024, and these results further support its efficacy in transforming the treatment landscape for BCG-unresponsive NMIBC.last yearNovel Agents Show Promise in BCG-Unresponsive NMIBC Treatment• TAR-200 monotherapy demonstrated an 83.5% complete response rate in the SunRISe-1 trial, with an estimated 12-month duration of response rate of 65.7%.
• Pembrolizumab monotherapy in the KEYNOTE-057 trial achieved a 41% complete response rate at 3 months in high-risk NMIBC patients without carcinoma in situ.
• Nadofaragene firadenovec-vncg showed a 53.4% complete response rate at 3 months and 45.5% at 1 year in a phase 3 trial for BCG-unresponsive NMIBC.
• Nogapendekin alfa inbakicept-pmln plus BCG achieved a 71% complete response rate at any time, with a median follow-up of 23.9 months in the QUILT-3.032 trial.last year